The NRF2 protein was discovered in 1994. Most importantly, it has significant roles in cellular regulation and detoxification. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcription factor for cellular defense against oxidative stress and a regulator of the expression of many antioxidant and detoxification genes.

According to Gaia Skibinski, one of its discoverers, the NRF2 protein was tested in two models of Parkinson's disease, demonstrating that by activating it, not only were various cleansing mechanisms within the cell turned on to eliminate the mutations that cause the disease, but it also protected the cells against the pathology.

NRF2 is found in the cell cytoplasm, bound to a protein called KEAP1 (Kelch-like ECH-associated protein 1), which keeps it inactive. Upon detecting oxidative stress or certain toxic chemical substances, NRF2 is released from KEAP1 and translocates to the nucleus, where it binds to antioxidant response elements (ARE) in the DNA. Through a complex network, it regulates cellular defense against toxic attacks, performs drug detoxification, and fights oxidative stress through gene expression, making cells resistant to chemical carcinogens and inflammatory processes.

NRF2 differentially regulates muscle glycogen metabolism, lipid metabolism, provides an antioxidant response, and maintains homeostasis.
Activation of NRF2 in mouse liver increases glycogen accumulation, which contributes to maintaining blood glucose levels during fasting.
The NRF2 protein stimulates the production of antioxidants, detoxifying enzymes that clear cells of toxic waste, and repair enzymes. It also activates various mechanisms that inhibit inflammation.
These effects benefit all cells, tissues, and organs of the human body. They especially benefit the brain, protecting it from reactive oxygen species and various toxic substances. It prevents cognitive decline and Alzheimer's disease.

Activation of the nuclear factor Nrf2 is a potential therapeutic target for neurodegeneration; it is estimated that it could reduce neuronal toxicity associated with Parkinson's Disease by modulating the protein homeostasis network.

Crucially, diet can significantly influence NRF2 activation. Several phytochemicals present in fruits, vegetables, spices, and other plant-based foods can induce NRF2 protein activity, promoting antioxidant resistance and cellular detoxification.
It has been proven that these phytochemicals activate the production of the Nrf2 protein, which stimulates the synthesis of the antioxidant glutathione peroxidase and other detoxifying and repair enzymes.
Some foods and dietary components studied for their ability to help activate NRF2 are:

• Sulforaphane, found in broccoli and other cruciferous vegetables, mustard greens, and radishes, is known for its anti-cancer and antioxidant properties and is a potent activator of the Nrf2 pathway. Sulforaphane promotes the release of NRF2 from the KEAP1 protein, facilitating its translocation to the nucleus and the activation of antioxidant genes. Sulforaphane's mechanism of action focuses on its ability to activate the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. This pathway is crucial for the regulation of antioxidant and detoxification genes. When sulforaphane activates Nrf2, a cellular response is produced that increases the production of protective and antioxidant enzymes, strengthening the body's defense system against oxidative damage. Sulforaphane also influences the expression of more than 200 genes related to inflammation, oxidative stress, and detoxification. This ability of sulforaphane to activate protective pathways is what makes it so valuable in promoting health and preventing disease.
• Turmeric, standardized to 95% curcuminoids, is another effective NRF2 activator. In addition to its anti-inflammatory properties, curcumin can increase the expression of detoxifying and protective genes against oxidative stress. A powerful anti-inflammatory and antioxidant. Curcumin has been shown to activate Nrf2 gene expression, which in turn stimulates the synthesis of antioxidants such as glutathione and detoxifying enzymes, thereby contributing to protection against oxidative stress and cellular damage.
• Green tea, which contains epigallocatechin gallate (EGCG), has been shown to induce NRF2 activity. Regular green tea consumption can offer antioxidant protection and reduce the risk of chronic diseases. Studies have shown that green tea can activate the Nrf2 pathway, suggesting that its regular consumption could help protect against cognitive decline and neurodegenerative diseases such as Alzheimer's.
• Fruits and berries, especially strawberries, raspberries, blueberries, and grapes (which contain pterostilbene), as well as pomegranates, which possess antioxidants such as anthocyanins and resveratrol, can activate NRF2 and improve the body's antioxidant capacity.
• Flax seeds, walnuts, and chia seeds are rich in omega-3 fatty acids and phenolic compounds, which can favor NRF2 activation and offer protection against inflammation and oxidative stress.

• Resveratrol, found in grape skins and seeds, activates NRF2 and protects against oxidative stress, apoptosis, inflammation, and cellular dysfunction caused by obesity; it is a potent antioxidant that can support cardiovascular health, reduce inflammation, and improve endothelial function. This compound has been the subject of numerous studies for its potential benefits to cardiovascular, brain, and metabolic health.
• Quercetin, from onions, apples, berries, and green tea, reduces inflammation, improves circulation, and has anti-allergic and cardioprotective properties.
• Silybin or silymarin, found in milk thistle, promotes the elimination of liver toxins.
• Vitamin D3 with Vit. K2, which, in addition to activating Nrf2, aids in bone and cardiovascular health and controls arterial calcification.
• The omega-3 fatty acid DHA, found in fatty fish such as salmon and sardines, has been shown to activate the Nrf2 protein, contributing to its anti-inflammatory and neuroprotective effects.
• Alpha-lipoic acid: beets, broccoli, carrots, potatoes, brewer's yeast, organ meats, and red meat.

In conclusion, phytochemicals that activate the production of the Nrf2 protein, such as curcumin, green tea extract, resveratrol, sulforaphane, and the omega-3 fatty acid DHA, can offer significant protection against oxidative stress and cellular damage throughout the human body, especially in the brain. These findings suggest that including foods and supplements rich in these phytochemicals in the regular diet could be an effective strategy to promote longevity and health, as well as to prevent chronic diseases related to oxidative stress. However, more research is needed to fully understand the underlying mechanisms and the specific benefits of each of these compounds on human health.